Trial Information

Predictive Modelling of Short Term Outcomes Following Systemic Neo-adjuvant and Adjuvant Therapy in Breast Cancer Patients

Patients with breast cancer are treated with a combination of surgery and medical treatment
(either before (neoadjuvant) or after (adjuvant) surgery). Eligible patients will be
identified by the oncologist and from the multidisciplinary meeting.

Once eligible patients have been identified they will be informed of the study by their
oncologist, and then approached by the research team who will give them a patient
information leaflet, discuss the study, answer any questions and ask the patient to sign a
consent form if they are would like to participate in the study. The consent form must be
signed before any study related procedures are performed.

Patients who have had surgery prior to receiving medical treatment (i.e. patients planned to
receive adjuvant treatment, or patients who have a sentinel lymph node biopsy prior to
starting neoadjuvant treatment) will have blood and urine samples taken before they have
their surgery, at the preassessment surgical appointment.

The week before the patient starts medical therapy (either chemotherapy or endocrine
treatment) the patient will need to attend Charing Cross Hospital for the following
procedures (this may be an extra visit, depending on hospital appointments):

- To see the study doctor for a medical history and physical examination

- Pulse and blood pressure measurements

- BMI (body mass index) and body fat assessment

- To fill out a quality of life (QOL) questionnaire with research staff

- Routine blood tests (for haematology and biochemistry)

- Blood sample for metabolic profiling and cytokine analysis

- Urine sample for metabolic profiling

- The blood taken will additionally be tested for targeted genetic analysis if the
patient has consented for this (as this is optional)

The patient will be asked to return to Charing Cross Hospital 24 hours later after an
overnight fast for (this will be an extra visit): • Fasted blood and urine samples for
metabolic profiling.

It is important to get fasted samples from patients, as diet influences the metabolic
profile. Therefore to try to eliminate diet as a confounder it is important to get a fasted
sample. Additionally, at the time of collection of blood and urine samples for metabolic
profile analysis patients will be asked when they last ate, what they last ate and any
specific dietary preferences/requirements (i.e. vegetarian, gluten free diet).

Further tests differ depending on whether the patient is receiving chemotherapy or endocrine
treatment.

Patients receiving chemotherapy have 6 cycles, each cycle last 21 days. There are two types
of chemotherapy given for breast cancer which are FEC (6 cycles of 5fluorouracil, epirubicin
and cyclophosphamide) or FECD (3 cycles of 5fluorouracil, epirubicin and cyclophosphamide
followed by 3 cycles of docetaxel). Patients receiving all types of chemotherapy (FEC and
FECD) patients will be required to attend at the following time for procedures are explained
below:

- Cycle 1, day 2

o 24 hours after the patient received their chemotherapy treatment we will take urine
and blood samples for metabolic profiling, and blood samples for routine blood tests
(haematology and biochemistry) and cytokine analysis.

- At this time the patient will also be asked to fill out 2 questionnaires with
research staff - the first will be adverse effects experienced (questions from
CTCAEv4.0), and the second will be a QOL questionnaire.

- This will be an extra visit.

- Cycle 2, day 1

- Prior to receiving their next cycle of chemotherapy urine and blood samples will
be taken for metabolic profiling. Blood samples will be taken for routine tests
(haematology and biochemistry) and for cytokine analysis.

- Two questionnaires (questionnaire based on adverse effects experienced and QOL
questionnaire) will be completed with research staff.

- A blood sample will be taken after 10 minutes chemotherapy infusion has finished.
Pharmacokinetic analysis for 5FU will be conducted on this sample. If possible the
sample will be taken from the cannula through which the chemotherapy medication
was administered (the first 10mls will need to be discarded to avoid
contamination).

- This will not be an extra visit if there has been no change to planned This will
not be an extra visit if there has been no change to planned treatment schedule.
If patients have consented for optional pharmacokinetic analysis the following
sample will also be taken.

- Cycle 2, day 1 (optional assessment)

o Three blood samples will be taken during the following 4 hours for pharmacokinetic
analysis of cylophosphamide and epirubicin. If possible all samples will be taken from
the cannula through which the chemotherapy was administered.

- Cycle 2, day 2 (optional assessment) o A blood sample will be taken 24 hours after the
chemotherapy was given for pharmacokinetic analysis of cyclophosphamide.

- Cycle 2, day 3 (optional assessment)

o A blood sample will be taken 48 hours after the chemotherapy was given for
pharmacokinetic analysis of epirubicin.

- Cycle 6, day 21

- Two questionnaires (questionnaire based on adverse effects experienced and QOL
questionnaire) will be completed with research staff.

- BMI (body mass index) and body fat assessment.

- This will be an extra visit.

If patients are on FECD chemotherapy, they will attend at the above time points, but they
will additionally be asked to attend after their docetaxel has commenced. This is required
to test whether docetaxel has a different reaction in the body to the previous chemotherapy
given. Patients will be asked to attend at the following time points for the following
procedures:

- Cycle 4, day 2

o 24 hours after the patient received their chemotherapy treatment we will take urine
and blood samples for metabolic profiling, and blood samples for routine blood tests
(haematology and biochemistry) and cytokine analysis.

o Two questionnaires (questionnaire based on adverse effects experienced and QOL
questionnaire) will be completed with research staff

o This will be an extra visit

- Cycle 5, day 1

- Prior to receiving their next cycle of chemotherapy urine and blood samples will
be taken for metabolic profiling. Blood samples will be taken for routine tests
(haematology and biochemistry) and for cytokine analysis.

- Two questionnaires (questionnaire based on adverse effects experienced and QOL
questionnaire) will be completed with research staff.

- This will not be an extra visit if there has been no change to planned treatment
schedule.

If patients have consented for optional pharmacokinetic analysis the following sample will
also be taken.

• Cycle 5, day 1

o A blood sample will be taken at the end of the chemotherapy infusion and 6 hours after the
infusion completed. If possible the blood samples will be taken from the cannula (the first
10mls taken from the cannula will need to be discarded to avoid contamination).

Patients receiving endocrine treatment will be asked to attend at the following time points
after starting treatment for procedures listed below, in addition to baseline assessments
described above:

- Two questionnaires (questionnaire based on adverse effects experienced and QOL
questionnaire) will be completed with research staff.

- BMI (body mass index) and body fat assessment.

- A blood sample for pharmacokinetic analysis

- This will be an extra visit

All procedures and interviews will be conducted at Charing Cross Hospital. All patients will
be enrolled in the study for 5 months. However, for patients receiving chemotherapy, if
there has been a change in treatment schedule by the oncologist the time the patient will
spend in the study will be increased in accordance with changes made to treatment schedule
(i.e. if cycle 4 (docetaxel) is started 1 week late, then the time in the study will be 5
months and 1 week).

For patients receiving neoadjuvant treatment (chemotherapy or endocrine treatment before
surgery) we will look at imaging and pathology reports to establish how the tumour has
responded to treatment.

The results will be analysed and published (in both presentations and a peer reviewed
journal) at the end of the study. No patient identifiable information will be present in
these publications. As all tests are carried out for research purposes and will be of no
direct benefit to patients participating in this study, there are no plans to inform
patients of their individual results. Patients will be informed of the overall results from
the study that may result in a publication.

Type of Study:

Observational

Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

The primary outcome measure for the study is to determine the relationship between metabonomics spectrum and side effects from chemotherapy and endocrine therapy for patients receiving treatment for breast cancer.

Outcome Description:

To identify a pre-treatment metabolic profile to predict patients who will experience moderate to severe side effects.

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Charles Coombes

Investigator Role:

Principal Investigator

Investigator Affiliation:

Imperial College London

Authority:

United Kingdom: National Health Service

Study ID:

72393/271478/14/611

NCT ID:

NCT01563211

Start Date:

February 2012

Completion Date:

May 2014

Related Keywords:

Toxicity From Medication (Endocrine Treatment and Chemotherapy) Given for Breast Cancer Treatment.

breast cancer therapy

toxicity

side effect profile

Breast Neoplasms

Name

Location

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